The title of this project has been changed from "cell adhesion molecules in ocular inflammation" to "immunologic mechanisms of ocular disease" to refle the broadening scope of experiments to encompass the role of cell adhesion molecules and other immunologic factors, including cytokines, in the pathogenesis of ocular diseases, particularly uveitis, ocular malignancy, a ocular disease related to AIDS. In addition, this project was previously listed in the Laboratory of Immunology but is now listed in the Clinical Branch. The goal of this project is to study the immunologic mechanisms involved in the pathogenesis of ocular inflammation and ocular malignancy and to develop and test therapies based on these data. Recently, we have concentrated on the role of cell adhesion molecules and cytokines in the development of ocular inflammatory disease. Cell adhesion molecules (CAMs) are surface proteins important for antigen sensitization and the migration of leukocytes to sites of inflammation. We are currently investigating compounds that block CAMs as a treatment for uveitis and other ocular inflammatory diseases. During the past year, we showed that a single injection with a monoclonal antibody against the CAMs, lymphocyte function- associated antigen-1 (LFA-1) and Mac-1, can inhibit the development of uveitis by more than 66 percent. In contrast, treatment with a monoclonal antibody against a third CAM, vascular adhesion molecule-1 (VCAM-1) failed to inhibit in vivo disease. Antibodies against these cell adhesion molecul also inhibited lymphocyte proliferation in vitro by up to 70 percent. We also studied the role of interleukin-12 on the development of acute intraocular inflammation and showed that systemically administered antibody against IL-12 exacerbates the endotoxin-induced uveitis. Similarly, intraocular IL-12 inhibited disease. These data suggest that endotoxin- induced uveitis may be a TH2-dependent disease. Finally, we investigated the effect of a number of therapeutic agents in animal models of ocular inflammation. We demonstrated that MDL 28,842, an inhibitor of S-adenosyl- L-homocysteine hydrolase, decreases the ocular inflammation in animals with experimental autoimmune uveitis (EAU). In other experiments, we showed that topically administered heparin inhibits the development of allergic conjunctivitis induced by mast cell degranulation.